Diabetic microangiography resulting in progressive retinal and renal disease is one of the most important facets of diabetes. In spite of considerable evidence from animal models and scattered evidence from clinical studies that microangiopathy is secondary to the dysmetabolism of diabetes, doubts about the importance of strict control of hyperglycemia linger on. We propose to study prospectively an inception cohort of at least 50 randomized diabetic kidney recipients to test the hypothesis that strict diabetic control prevents or delays the emergence of diabetic nephropathy, which we have reported to occur two to four years after transplant of healthy kidneys into diabetics. The design of this study is unique in that a) an inception cohort is available, b) careful prerandomization matching followed by randomization will be undertaken, c) prospective follow-up for seven years is planned, d) "strict diabetic treatment" in the experimental group will be compared with a control group on "standard diabetic treatment," e) metabolic control in the experimental group will be painstakingly implemented with three daily injections of insulin matched with the meals and very close contact with the patients, f) the degree of metabolic control will be objectively evaluated by a scoring system and frequent determinations of various parameters of metabolic control including plasma and urine glucose, blood fats, hemoglobin AIc, 2, 3-DPG, etc., in both groups of patients, and g) the end points of thickened renal gl merular basement membrane and mesangium, immunopathology of renal extracellular membranes, and glomerular arteriolar hyalinosis will be studied in biopsy material at two and five years.